IL294608A - Methods and compositions for delivery of immunotherapy agents across the blood-brain barrier to treat brain cancer - Google Patents

Methods and compositions for delivery of immunotherapy agents across the blood-brain barrier to treat brain cancer

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Publication number
IL294608A
IL294608A IL294608A IL29460822A IL294608A IL 294608 A IL294608 A IL 294608A IL 294608 A IL294608 A IL 294608A IL 29460822 A IL29460822 A IL 29460822A IL 294608 A IL294608 A IL 294608A
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IL
Israel
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seq
subject
sequence
immunotherapy agent
amino acids
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IL294608A
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Hebrew (he)
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Brigham & Womens Hospital Inc
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Publication of IL294608A publication Critical patent/IL294608A/en

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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • A61K31/175—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine having the group, >N—C(O)—N=N— or, e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
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    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
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    • C12N15/09—Recombinant DNA-technology
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    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
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    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
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    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
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    • C12N2750/14011—Parvoviridae
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Claims (16)

Attorney Docket No. 29618-0244WO WHAT IS CLAIMED IS:
1. A method of delivering an immunotherapy agent to a cancer in a subject, the method comprising administering to the subject an adeno-associated virus (AA V) comprising (i) a capsid protein comprising an amino acid sequence that comprises at least four contiguous amino acids from the sequence TVSALFK (SEQ ID NO:8); TVSALK (SEQ ID NO:4); KLASVT (SEQ ID NO:83); or KFLASVT (SEQ ID NO:84), and (ii) a transgene encoding an immunotherapy agent, optionally wherein the cancer cell is in the brain of a human subject.
2. The method of claim 1, wherein the amino acid sequence comprises at least five contiguous amino acids from the sequence TVSALK (SEQ ID NO:4); TVSALFK (SEQ ID NO:8); KLASVT (SEQ ID NO:83); or KFLASVT (SEQ ID NO:84).
3. The method of claim 1, wherein the amino acid sequence comprises at least six contiguous amino acids from the sequence TVSALK (SEQ ID NO:4); TVSALFK (SEQ ID NO:8); KLASVT (SEQ ID NO:83); or KFLASVT (SEQ ID NO:84).
4. A method of delivering an immunotherapy agent to a cancer in a subject, the method comprising administering to the subject an adeno-associated virus (AA V) comprising (i) a capsid protein comprising an amino acid sequence that comprises at least four contiguous amino acids from the sequence V[S/p][A/m/t/]L (SEQ ID NO:79), TV[S/p][A/m/t/]L (SEQ ID NO:80), TV[S/p][A/m/t/]LK (SEQ ID NO:81), or TV[S/p][A/m/t/]LFK. (SEQ ID NO:82), and (ii) a transgene encoding an immunotherapy agent, optionally wherein the cancer cell is in the brain of a human subject.
5. The method of claim 4, wherein the targeting sequence comprises VPALR (SEQ ID NO:1); VSALK (SEQ ID NO:2); TVPALR (SEQ ID NO:3); TVSALK (SEQ ID NO:4); TVPMLK (SEQ ID NO:12); TVPTLK (SEQ ID NO:13); FTVSALK (SEQ ID NO:5); LTVSALK (SEQ ID NO:6); TVSALFK (SEQ ID NO:8); TVPALFR (SEQ ID NO:9); TVPMLFK (SEQ ID NO:10) or TVPTLFK (SEQ ID NO:11). Attorney Docket No. 29618-0244WO
6. The method of claims 1-5, wherein the transgene encoding an immunotherapy agent encodes an antibody targeting PD-1 or PD-L1.
7. The method of claim 6, wherein the subject is a mammalian subject.
8. The method of claim 7, wherein the AA V is AA V9.
9. The method of claim 8, wherein the AA V9 comprises AA V9 VP1.
10. The method of claim 9, wherein the targeting sequence is inserted in a position corresponding to amino acids 588 and 589 of AAV9 VP1 comprising SEQ ID NO:85.
11. The method of claim 7, wherein the cell is in the brain of the subject, and the AA V is administered by parenteral delivery; intracerebral; or intrathecal delivery.
12. The method of claim 11, wherein the parenteral delivery is via intravenous, intraarterial, subcutaneous, intraperitoneal, or intramuscular delivery.
13. The method of claim 12, wherein the intrathecal delivery is via lumbar injection, cisternal magna injection, or intraparenchymal injection.
14. The method of any of claims 1-13, further comprising administering chemotherapy, radiation, and/or surgical resection to the subject.
15. The method of claim 14, wherein the chemotherapy comprises temozolamide, lomustine, or a combination thereof.
16. An adeno-associated virus (AA V) comprising (i) a capsid protein comprising an amino acid sequence that comprises at least four contiguous amino acids from the sequence TVSALFK (SEQ ID NO:8); TVSALK (SEQ ID NO:4); KLASVT (SEQ ID NO:83); or KFLASVT (SEQ ID NO:84), and (ii) a transgene encoding an immunotherapy agent for use in a method of delivering the immunotherapy agent to a cancer in a subject, wherein the method comprises administering to the subject the AA V and the transgene encoding the immunotherapy agent, optionally wherein the cancer cell is in the brain of a human subject.
IL294608A 2020-01-10 2021-01-08 Methods and compositions for delivery of immunotherapy agents across the blood-brain barrier to treat brain cancer IL294608A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202062959625P 2020-01-10 2020-01-10
PCT/US2021/012746 WO2021142300A2 (en) 2020-01-10 2021-01-08 Methods and compositions for delivery of immunotherapy agents across the blood-brain barrier to treat brain cancer

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IL294608A true IL294608A (en) 2022-09-01

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US (1) US11981705B2 (en)
EP (1) EP4087602A4 (en)
JP (1) JP2023510784A (en)
KR (1) KR20220127847A (en)
CN (1) CN115279400A (en)
AU (1) AU2021206256A1 (en)
CA (1) CA3167290A1 (en)
IL (1) IL294608A (en)
WO (1) WO2021142300A2 (en)

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